SYNERGY
LMWHLMWH
ESSENCEESSENCE
19941994 19951995 19961996 19971997 19981998 19991999 20002000 20022002 20032003 20042004 20052005 2006200620012001
CURECURE
ClopidogrelClopidogrel
Bleeding riskBleeding risk
Ischemic riskIschemic risk
GP IIb/IIIa GP IIb/IIIa blockersblockers
PRISM-PLUSPRISM-PLUS
PURSUITPURSUIT
ACUITYTACTICS TIMI-18TACTICS TIMI-18
Early invasiveEarly invasive
PCIPCI ~ 5% stents~ 5% stents ~85% stents~85% stents Drug-eluting stentsDrug-eluting stents
ISAR-REACT 2
Milestones in ACS Management
OASIS-5
[ Fondaparinux ][ Fondaparinux ]
Anti-Thrombin RxAnti-Thrombin Rx
Anti-Platelet RxAnti-Platelet Rx
Treatment StrategyTreatment Strategy
HeparinHeparin
AspirinAspirin
ConservativeConservative
ICTUS
BivalirudinBivalirudin
REPLACE 2REPLACE 2
Ischemic Complications Ischemic
Complications
► Death
► MI
► Urgent TVR
► Death
► MI
► Urgent TVR
Evolving Paradigm for Evaluating ACS Evolving Paradigm for Evaluating ACS Management StrategiesManagement Strategies
Composite Adverse Event EndpointsComposite Adverse Event Endpoints
Ischemic Complications Ischemic
Complications Hemorrhage HIT
Hemorrhage HIT
► Death
► MI
► Urgent TVR
► Death
► MI
► Urgent TVR
► Major Bleeding
► Minor Bleeding
► Thrombocytopenia
► Major Bleeding
► Minor Bleeding
► Thrombocytopenia
Composite Adverse Event EndpointsComposite Adverse Event Endpoints
Evolving Paradigm for Evaluating ACS Evolving Paradigm for Evaluating ACS Management StrategiesManagement Strategies
Evolving Paradigm for Evaluating ACS Evolving Paradigm for Evaluating ACS Management StrategiesManagement Strategies
Risk of events
Risk of bleeding
ThrombosisHemostasis
Two sides of the same coin
Degree of Anticoagulation
Ris
k
Balancing Events and BleedingBalancing Events and BleedingBalancing Events and BleedingBalancing Events and Bleeding
DeathDeath 4.3%4.3%
(Re)-Infarction(Re)-Infarction 2.5%2.5%
CHFCHF 8.0%8.0%
Cardiogenic ShockCardiogenic Shock 2.6%2.6%
StrokeStroke 0.8%0.8%
Non-CABG TransfusionNon-CABG Transfusion 9.9%9.9%
Bhatt DL, et al. Bhatt DL, et al. JAMAJAMA. 2004 Nov 3;292(17):2096-104. . 2004 Nov 3;292(17):2096-104.
CRUSADE In-Hospital OutcomesCRUSADE In-Hospital Outcomes
Quali sono i pazienti a rischio di
sanguinamento?
Quali sono i pazienti a rischio di
sanguinamento?
Bleeding in ACS
Domanda:Domanda:
Independent Independent Predictors of Predictors of Major Bleeding Major Bleeding in in Acute Coronary Acute Coronary SyndromesSyndromes
Moscucci, GRACE Registry, Moscucci, GRACE Registry, Eur Heart JEur Heart J. 2003 Oct;24(20):1815-23. . 2003 Oct;24(20):1815-23.
Predictors of Major Bleeding in ACSPredictors of Major Bleeding in ACS
► Older AgeOlder Age
► Female GenderFemale Gender
► Renal FailureRenal Failure
► History of BleedingHistory of Bleeding
► Right Heart CatheterizationRight Heart Catheterization
► GPIIb-IIIa antagonistsGPIIb-IIIa antagonists
P-valueP-valueRR (95% CI)RR (95% CI)Risk ratio ± 95% CIRisk ratio ± 95% CIRisk ratio ± 95% CIRisk ratio ± 95% CI
Predictors of Major BleedingPredictors of Major Bleeding
Age Age >>75 (vs. 55-75)75 (vs. 55-75)
AnemiaAnemia
CrCl <60mL/minCrCl <60mL/min
DiabetesDiabetes
Female genderFemale gender
High-risk (ST / biomarkers)High-risk (ST / biomarkers)
HypertensionHypertension
Heparin(s) + GPI (vs. Bivalirudin)Heparin(s) + GPI (vs. Bivalirudin)
1.56 (1.19-2.04)1.56 (1.19-2.04) 0.00090.0009
1.89 (1.48-2.41)1.89 (1.48-2.41) <0.0001<0.0001
1.68 (1.29-2.18)1.68 (1.29-2.18) <0.0001<0.0001
1.30 (1.03-1.63)1.30 (1.03-1.63) 0.02480.0248
2.08 (1.68-2.57)2.08 (1.68-2.57) <0.0001<0.0001
1.42 (1.06-1.90)1.42 (1.06-1.90) 0.01780.0178
1.33 (1.03-1.70)1.33 (1.03-1.70) 0.02870.0287
2.08 (1.56-2.76)2.08 (1.56-2.76) <0.0001<0.0001
Manoukian SV, Voeltz MD, Feit F et al. TCT 2006.
Results: The ACUITY Trial PCI PopulationResults: The ACUITY Trial PCI PopulationResults: The ACUITY Trial PCI PopulationResults: The ACUITY Trial PCI Population
MA…MA…
REPLACE-2REPLACE-2Multivariate Predictors of Major BleedingMultivariate Predictors of Major Bleeding
RISK FACTORSRISK FACTORS Odds RatioOdds Ratio 95% CI95% CI p-valuep-value
Baseline risk factorsBaseline risk factors
Age Age >> 75 75 1.4821.482 1.009 to 2.1761.009 to 2.176 0.0450.045
Gender (M vs. F)Gender (M vs. F) 0.6520.652 0.477 to 0.8900.477 to 0.890 0.00720.0072
Prior AnginaPrior Angina 1.5891.589 1.077 to 2.3451.077 to 2.345 0.01970.0197
Creatinine clearance* Creatinine clearance* 0.9930.993 0.987 to 0.9980.987 to 0.998 0.00610.0061
AnemiaAnemia 1.4031.403 1.015 to 1.9391.015 to 1.939 0.04010.0401
Peri-procedural risk factorsPeri-procedural risk factors
Treatment Group (BIV vs. H+GPI)Treatment Group (BIV vs. H+GPI) 0.5080.508 0.352 to 0.7330.352 to 0.733 0.00030.0003
Provisional GPI receivedProvisional GPI received 2.6792.679 1.591 to 4.5121.591 to 4.512 0.00020.0002
Procedure Duration >1hProcedure Duration >1h 2.0492.049 1.217 to 3.4491.217 to 3.449 0.00690.0069
Time to Sheath Removal >6hTime to Sheath Removal >6h 1.6141.614 1.064 to 2.4481.064 to 2.448 0.02440.0244
ICU stay (days)†ICU stay (days)† 1.251.25 1.183 to 1.3211.183 to 1.321 <0.0001<0.0001
IABPIABP 8.7058.705 3.433 to 22.0723.433 to 22.072 <0.0001<0.0001Feit F et al.
Il sanguinamento influenza la prognosi
del paziente?
Il sanguinamento influenza la prognosi
del paziente?
Bleeding in ACS
Domanda:Domanda:
Moscucci M et al. Moscucci M et al. Eur Heart JEur Heart J 2003;24:1815-23. 2003;24:1815-23.
P<0.001
Overall Unstable NSTEMI STEMIOverall Unstable NSTEMI STEMI ACS AnginaACS Angina
Pat
ien
ts (
%)
Pat
ien
ts (
%)
Major Bleeding Predicts Mortality in ACSMajor Bleeding Predicts Mortality in ACSMajor Bleeding Predicts Mortality in ACSMajor Bleeding Predicts Mortality in ACS
24,045 ACS patients in the GRACE registry, in-hospital death24,045 ACS patients in the GRACE registry, in-hospital death24,045 ACS patients in the GRACE registry, in-hospital death24,045 ACS patients in the GRACE registry, in-hospital death
log rank p-value for all four categories <0.0001log-rank p-value for no bleeding vs. mild bleeding = 0.02log-rank p-value for mild vs. moderate bleeding <0.0001log-rank p-value for moderate vs. severe <0.001
Bleeding & OutcomesBleeding & Outcomes
Rao SV, et al. Rao SV, et al. Am J CardiolAm J Cardiol. 2005 Nov 1;96(9):1200-6. Epub 2005 Sep 12 . 2005 Nov 1;96(9):1200-6. Epub 2005 Sep 12 Rao SV, et al. Rao SV, et al. Am J CardiolAm J Cardiol. 2005 Nov 1;96(9):1200-6. Epub 2005 Sep 12 . 2005 Nov 1;96(9):1200-6. Epub 2005 Sep 12
Kaplan Meier Curves for 30-Day Death, Stratified by Bleed SeverityKaplan Meier Curves for 30-Day Death, Stratified by Bleed Severity
N=26,452 ACS patients from GUSTO IIb, PARAGON A, PARAGON B, & PURSUIT N=26,452 ACS patients from GUSTO IIb, PARAGON A, PARAGON B, & PURSUIT
Major Bleeding, Ischemic Endpoints, Major Bleeding, Ischemic Endpoints, and Mortalityand Mortality
P<0.0001 for all
Manoukian SV, Voeltz MD, Feit F et al. TCT 2006.
Results: The ACUITY Trial PCI Population (N=7,789)Results: The ACUITY Trial PCI Population (N=7,789)Results: The ACUITY Trial PCI Population (N=7,789)Results: The ACUITY Trial PCI Population (N=7,789)
Major and Minor Bleeding in PCIMajor and Minor Bleeding in PCIBleeding Increases Mortality and EventsBleeding Increases Mortality and Events
Kinnaird TD et al. AM J Cardiol 2003;92:930-5.
10,974 patients undergoing PCI, Washington Hospital Center, 1991-2000.
In-Hospital Clinical EventsIn-Hospital Clinical Events
MajorMajor(n=588)(n=588)
MinorMinor(n=1,394)(n=1,394)
NoneNone(n=8,992)(n=8,992)
DeathDeath 7.5%*7.5%*†† 1.8%*1.8%* 0.6%0.6%
Q-wave myocardial infarctionQ-wave myocardial infarction 1.2%*1.2%* 0.7%0.7%‡‡ 0.2%0.2%
Non-Q-wave myocardial infarctionNon-Q-wave myocardial infarction 30.7%*30.7%*†† 16.8%*16.8%* 11.8%11.8%
Repeat lesion angioplastyRepeat lesion angioplasty 1.9%*1.9%*§§ 0.8%0.8%‡‡ 0.3%0.3%
Major adverse cardiac eventMajor adverse cardiac event 6.6%*6.6%*†† 2.2%*2.2%* 0.6%0.6%
Bleeding ComplicationBleeding Complication
* p<0.001 versus none † p<0.001 versus minor ‡ p<0.01 versus none § p<0.05 versus minor
Come valutare l’entità del
sanguinamento?
Come valutare l’entità del
sanguinamento?
Bleeding in ACS
Domanda:Domanda:
Bleeding Incidence in ACS Clinical TrialsBleeding Incidence in ACS Clinical Trials
Rao SV, et al. J Am Coll Cardiol. 2006 Feb 21;47(4):809-16. Epub 2006 Jan 26 Rao SV, et al. J Am Coll Cardiol. 2006 Feb 21;47(4):809-16. Epub 2006 Jan 26
Bleeding DefinitionsBleeding Definitions
► TIMI DefinitionTIMI Definition MajorMajor
• ICHICH• Associated with Hgb decrease ≥ 5 g/dl or Associated with Hgb decrease ≥ 5 g/dl or
HCT decrease ≥ 15%HCT decrease ≥ 15% MinorMinor
• Observed blood loss associated with Hgb Observed blood loss associated with Hgb decrease ≥ 3 g/dl or HCT decrease ≥ 10%decrease ≥ 3 g/dl or HCT decrease ≥ 10%
• No identifiable source but Hgb decrease No identifiable source but Hgb decrease ≥ 4 g/dl or HCT decrease ≥ 12%≥ 4 g/dl or HCT decrease ≥ 12%
MinimalMinimal• Overt hemorrhage with Hgb drop < 3 g/dl or Overt hemorrhage with Hgb drop < 3 g/dl or
HCT drop < 9%HCT drop < 9%
Chesebro JH. Chesebro JH. CirculationCirculation 1987. Jul;76(1):142-54. 1987. Jul;76(1):142-54. Chesebro JH. Chesebro JH. CirculationCirculation 1987. Jul;76(1):142-54. 1987. Jul;76(1):142-54.
N Engl J MedN Engl J Med. 1993 Nov 25;329(22):1615-22. Erratum in: . 1993 Nov 25;329(22):1615-22. Erratum in: N Engl J MedN Engl J Med 1994 Feb 17;330(7):516 1994 Feb 17;330(7):516 N Engl J MedN Engl J Med. 1993 Nov 25;329(22):1615-22. Erratum in: . 1993 Nov 25;329(22):1615-22. Erratum in: N Engl J MedN Engl J Med 1994 Feb 17;330(7):516 1994 Feb 17;330(7):516
Bleeding DefinitionsBleeding Definitions
► GUSTO DefinitionGUSTO Definition Severe or life threateningSevere or life threatening
• ICH or hemodynamic compromise ICH or hemodynamic compromise requiring treatmentrequiring treatment
ModerateModerate• Requiring transfusionRequiring transfusion
MildMild• Not meeting criteria for Severe or Not meeting criteria for Severe or
ModerateModerate
Bleeding Scales Among Bleeding Scales Among NSTE ACS PatientsNSTE ACS Patients
Rao SV, et al. J Am Coll Cardiol. 2006 Feb 21;47(4):809-16. Epub 2006 Jan 26 Rao SV, et al. J Am Coll Cardiol. 2006 Feb 21;47(4):809-16. Epub 2006 Jan 26
TIMI and GUSTO – Adjusted Hazard of 30 d Death/MI N=15,858TIMI and GUSTO – Adjusted Hazard of 30 d Death/MI N=15,858TIMI and GUSTO – Adjusted Hazard of 30 d Death/MI N=15,858TIMI and GUSTO – Adjusted Hazard of 30 d Death/MI N=15,858
► La trasfusione ha un impatto sulla
prognosi?
► La trasfusione è in grado di correggere
l’effetto negativo del sanguinamento?
► La trasfusione ha un impatto sulla
prognosi?
► La trasfusione è in grado di correggere
l’effetto negativo del sanguinamento?
Bleeding in ACS
Domanda:Domanda:
30-Day Survival By Transfusion Group30-Day Survival By Transfusion Group
Rao SV, et. al., Rao SV, et. al., JAMAJAMA 2004;292:1555–1562 2004;292:1555–1562Rao SV, et. al., Rao SV, et. al., JAMAJAMA 2004;292:1555–1562 2004;292:1555–1562
Transfusion in ACSTransfusion in ACS
N=24,111N=24,111N=24,111N=24,111
METANALYSIS OF the GUSTOIIb,PURSUIT,and PARAGON b trials
METANALYSIS OF the GUSTOIIb,PURSUIT,and PARAGON b trials
*Transfusion as a time-dependent covariate*Transfusion as a time-dependent covariate
PRBC Transfusion Among NSTE ACS Patients:PRBC Transfusion Among NSTE ACS Patients:Cox Model for 30-day DeathCox Model for 30-day Death
Rao SV, et. al., Rao SV, et. al., JAMAJAMA 2004;292:1555–1562 2004;292:1555–1562Rao SV, et. al., Rao SV, et. al., JAMAJAMA 2004;292:1555–1562 2004;292:1555–1562
N=24,111N=24,111N=24,111N=24,111METANALYSIS OF the GUSTOIIb,PURSUIT,and PARAGON b trials
METANALYSIS OF the GUSTOIIb,PURSUIT,and PARAGON b trials
Adjusted Risk of In-Hospital Outcomes Adjusted Risk of In-Hospital Outcomes
By Transfusion Status*By Transfusion Status*
*Non-CABG patients onlyYang X, Yang X, J Am Coll CardiolJ Am Coll Cardiol 2005;46:1490–5. 2005;46:1490–5.Yang X, Yang X, J Am Coll CardiolJ Am Coll Cardiol 2005;46:1490–5. 2005;46:1490–5.
N=74,271 ACS patients from CRUSADEN=74,271 ACS patients from CRUSADE
Increased 1-year mortality in transfused patientsIncreased 1-year mortality in transfused patientsAdjusted Odds Ratio 4.26 (2.25–8.08)Adjusted Odds Ratio 4.26 (2.25–8.08)
Transfusion Post PCI:Transfusion Post PCI:REPLACE 2 One Year MortalityREPLACE 2 One Year Mortality
P<0.0001
Manoukian SV, Voeltz MD, Attubato MJ, Bittl JA, Feit F, Lincoff AM. CRT 2005. Abstract.
“storage lesions”:
aumento fragilità di membrana (ridotta deformabilità)
alterata capacità di trasporto dell’ossigeno
pH ridotto
riduzione del n° cellule vitali/unità
aumento delle citochine pro-infiammatorie (leucociti contaminanti)
alterata biologia dell’NO nel sangue conservato
bassi livelli di 2,3 difosfoglicerati -> aumentata affinità dell’O2
per l’Hb
EMOTRASFUSIONI NEGLI ANZIANI CON IMA
Wu W-C NEJM 2001;345:1230
78.974 pz Medicare con IMA > 65 aa
ematocrito (%)
OR (95% CI) di morte < 30 gg con aggiustamento per i fattori clinici, i farmaci e i predittori di trasfusioni
5.0 – 24.0 0.22 (0.11 - 0.45)
24.1 – 27.0 0.48 (0.34 – 0.69)
27.1 – 30.0 0.60 (0.47 – 0.76)
30.1 – 33.0 0.69 (0.53 – 0.89)
33.1 – 36.0 1.13 (0.89 – 1.44)
36.1 – 39.0 1.38 (1.05 – 1.80)
39.1 – 38.0 1.46 (1.18 – 1.81)
High Risk Patient Subgroups
Bleeding Risks—Transfusions by AgeBleeding Risks—Transfusions by Age
Alexander KA, Alexander KA, JAMAJAMA 2005;294:3108–16. 2005;294:3108–16. Alexander KA, Alexander KA, JAMAJAMA 2005;294:3108–16. 2005;294:3108–16.
6,002 patients in REPLACE-26,002 patients in REPLACE-2806 patients (13.4%) classified as elderly, >75 years of age806 patients (13.4%) classified as elderly, >75 years of age
p<0.0001 p=0.0001
REPLACE-2:REPLACE-2:Elderly Patients Have Increased Major Bleeding and Elderly Patients Have Increased Major Bleeding and
TransfusionsTransfusions
= Not Elderly, <75
= Elderly, >75
Voeltz MD, Lincoff AM, Feit F, Manoukian SV. Circulation 2005;112(17):II-613. Abstract.
p<0.0001 p=0.0001
6,002 patients in REPLACE-2.6,002 patients in REPLACE-2. 806 patients (13.4%) classified as elderly, >75 years of age.806 patients (13.4%) classified as elderly, >75 years of age.
Elderly Patients in REPLACE-2:Elderly Patients in REPLACE-2:Increased 30-Day Mortality With Major Bleeding and TransfusionsIncreased 30-Day Mortality With Major Bleeding and Transfusions
Voeltz MD, Lincoff AM, Feit F, Manoukian SV. Circulation 2005;112(17):II-613. Abstract.
Excessive Dosing ofExcessive Dosing ofAnticoagulants by AgeAnticoagulants by Age
Alexander KA, Alexander KA, JAMAJAMA 2005;294:3108–16. 2005;294:3108–16. Alexander KA, Alexander KA, JAMAJAMA 2005;294:3108–16. 2005;294:3108–16.
12.5
28.7
8.5
33.137
12.5
64.5
38.5
16.5
0
10
20
30
40
50
60
70
LMW Heparin UF Heparin GP Iib/IIIa
% E
xcse
ssiv
e d
ose
<65 yrs 65-75 yrs >75 yrs
Excess Dosing of Gp IIb/IIIa Excess Dosing of Gp IIb/IIIa and Bleeding in Womenand Bleeding in Women
OverallOverallOverallOverall
WomenWomenWomenWomen
MenMenMenMen
1.46 (1.22, 1.73)1.46 (1.22, 1.73)1.46 (1.22, 1.73)1.46 (1.22, 1.73)
1.72 (1.30, 2.28)1.72 (1.30, 2.28)1.72 (1.30, 2.28)1.72 (1.30, 2.28)
1.27 (0.97, 1.66)1.27 (0.97, 1.66)1.27 (0.97, 1.66)1.27 (0.97, 1.66)
0.50.50.50.5 1.01.01.01.0 1.51.51.51.5 2.02.02.02.0 2.52.52.52.5
Excess Dosing More Likely to BleedExcess Dosing More Likely to BleedExcess Dosing More Likely to BleedExcess Dosing More Likely to Bleed
Alexander KP, et. al. Circulation 2006Alexander KP, et. al. Circulation 2006
N=32,601 patients from CRUSADEN=32,601 patients from CRUSADEN=32,601 patients from CRUSADEN=32,601 patients from CRUSADE
Bleeding is Increased in Patients With Bleeding is Increased in Patients With Impaired Renal Function Undergoing PCIImpaired Renal Function Undergoing PCI
≥≥ 60 ml/min60 ml/min N=4824 N=4824
< 60 ml/min< 60 ml/min N=886 N=886 p valuep value
30-d Death30-d Death 5 (0.1%)5 (0.1%) 14 (1.6%)14 (1.6%) < 0.001< 0.001
30-d Myocardial infarction30-d Myocardial infarction 305 (6.3%)305 (6.3%) 75 (8.5%)75 (8.5%) 0.0180.018
30-d urgent revascularization30-d urgent revascularization 61 (1.3%)61 (1.3%) 10 (1.1%)10 (1.1%) 0.7380.738
Triple ischemic endpointTriple ischemic endpoint 338 (7.0%)338 (7.0%) 84 (9.5%)84 (9.5%) 0.0100.010
In-hospital protocol major In-hospital protocol major bleedingbleeding 123 (2.5%)123 (2.5%) 54 (6.1%)54 (6.1%) < 0.001< 0.001
TIMI major + minor bleedingTIMI major + minor bleeding 114 (2.4%)114 (2.4%) 46 (5.2%)46 (5.2%) < 0.001< 0.001
Creatinine ClearanceCreatinine Clearance
Chew DP et al. Am J Cardiol 2005;95:581–585.
enoxaparin CrCl < 30 controindicata o dose
fondaparinux CrCl < 30controindicata – tuttavia emorragie vs enox
bivalirudinCrCl < 30emodialisi
dose 1 mg/kg/h dose 0.25 mg/kg/h
tirofiban CrCl < 30 dose 50 %
eptifibatideCrCl < 50 < 30
dose 50 % controindicato
abciximabvalutazione attenta del rischio emorragico
farmaci antitrombotici e antiaggreganti, insufficienza renale e
rischio emorragico
Major Bleeding is IncreasedMajor Bleeding is Increasedin Anemic Patients Undergoing PCIin Anemic Patients Undergoing PCI
6,010 patients in REPLACE-2.1,362 patients (22.7%) classified as anemic based upon WHO definition.
Major bleeding = 3.2%
Major Bleeding
2.8%
4.9%
P=0.0001
Protocol definition: >3g/dL drop in HgB,
intracranial, retroperitoneal,
2U transfusion
Voeltz MD, Attubato MJ, Feit F, Lincoff AM, Manoukian SV. J Am Coll Cardiol 2005;45(3)[Suppl Voeltz MD, Attubato MJ, Feit F, Lincoff AM, Manoukian SV. J Am Coll Cardiol 2005;45(3)[Suppl A]:1037-13-31A. Abstract.A]:1037-13-31A. Abstract.
NSTE-ACS MortalityNSTE-ACS MortalityStratified by HemoglobinStratified by Hemoglobin
Sabatine MS. Circulation 2005
UnadjustedUnadjusted
Hb (g/dL)Hb (g/dL) nn OROR (95% Cl)(95% Cl) OROR (95% Cl)(95% Cl) P P valuevalue
>17>17 216 216 1.471.47 (1.03–2.10)(1.03–2.10) 1.451.45 (0.94–2.23)(0.94–2.23) 0.0930.093
16–1716–17 812 812 1.211.21 (0.97–1.51)(0.97–1.51) 1.271.27 (0.98–1.65)(0.98–1.65) 0.0660.066
15–1615–16 21302130 1.0 1.0 referencereference 1.0 1.0 referencereference
14–1514–15 33903390 1.061.06 (0.89–1.22)(0.89–1.22) 1.111.11 (0.93–1.33)(0.93–1.33) 0.2510.251
13–1413–14 35203520 1.021.02 (0.88–1.19)(0.88–1.19) 1.041.04 (0.86–1.24)(0.86–1.24) 0.7090.709
12–1312–13 23312331 1.091.09 (0.92–1.28)(0.92–1.28) 1.071.07 (0.88–1.30)(0.88–1.30) 0.5140.514
11–1211–12 976 976 1.201.20 (0.97–1.47)(0.97–1.47) 1.041.04 (0.81–1.34)(0.81–1.34) 0.7550.755
10–1110–11 343 343 1.411.41 (1.05–1.89)(1.05–1.89) 1.291.29 (0.92–1.82)(0.92–1.82) 0.1450.145
9–109–10 342 342 2.442.44 (1.88–3.18)(1.88–3.18) 2.692.69 (2.01–3.60)(2.01–3.60) <0.001<0.001
8–98–9 306 306 2.242.24 (1.69–2.96)(1.69–2.96) 2.452.45 (1.80–3.33)(1.80–3.33) <0.001<0.001
<8<8 137 137 3.973.97 (2.76–5.70)(2.76–5.70) 3.493.49 (2.35–5.20)(2.35–5.20) <0.001<0.001
Abbreviations: CI, confidence interval; Hb, hemoglobin; OR, odds ration. Adapted with permission.Abbreviations: CI, confidence interval; Hb, hemoglobin; OR, odds ration. Adapted with permission.
Unadjusted and adjusted odds ratios for cardiovascular mortality in patientsUnadjusted and adjusted odds ratios for cardiovascular mortality in patientswith non-ST elevation acute coronary syndromes at 30 days stratefied by hemoglobinwith non-ST elevation acute coronary syndromes at 30 days stratefied by hemoglobin
Adjusted for baseline characteristicsAdjusted for baseline characteristics
indicazioni alla trasfusione di piastrine
Shander A Pharmacotherapy 2007;27(9 Pt 2):57S
piastrinopenia severa (< 50 x 103/mmc) in caso di sanguinamento attivo
prevenzione del sanguinamento in caso di piastrinopenia molto severa
(< 5-10 x 103/mmc)
piastrinopenia severa (< 50 x 103/mmc) prima di una procedura invasiva
prevenzione del sanguinamento spontaneo in pazienti con piastrinopenia
severa (<10-50 x 103/mmc), in caso di sepsi, uso di antibiotici, altre anoma-
lie della coagulazione
nei disordini della funzione piastrinica (uremia, tromboastenia, farmaci
antipiastrinici), in caso di sanguinamento attivo.
E’ causata da anticorpi diretti contro il complesso PF4 piastrinico ed eparina
Compare dopo circa 5-10 giorni dall’ inizio della terapia in pazienti non precedentemente esposti (oltre 100 gg), in poche ore se vi è stato un recente trattamento
Può essere molto severa anche valori inferiori a 10.000 per mmc, con lenta risalita (4-14 gg), dopo la sospensione del farmaco.
E’ raramente associata a fenomeni emorragici, invece predominano le complicanze trombotiche (25-50% dei pz) con un rischio di trombosi 30 volte maggiore che nella popolazione di controllo
E’ 10 volte più frequente nei pz trattati con UHF vs LMWH
Se sospetto clinico ricerca di anticorpi per il complesso PF4-eparina, eventuale test funzionali di aggregazione piastrinica
-> sospensione della terapia eparinica
-> anticoagulazione
1. Associazione temporale
2. Nova insorgenza di trombosi
3. Risalita dopo sospensione
dosaggio ASA (+ clopidogrel) ed emorragie - CURE -
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